A Phase III, randomized, two-armed, parallel, double-blind, active-controlled, equivalence clinical trial to compare efficacy and safety of test-Tocilizumab (AryoGen Pharmed, Iran) to the reference Tocilizumab product (Actemra®, Genentech, USA) in patients with moderate to severe active rheumatoid arthritis

Inclusion criteria:

Male or female aged 18 –65 years at the time of signing the informed consent form Have been diagnosed as having rheumatoid arthritis for at least 6 months, using the 2010 American College of Rheumatology/European League Against Rheumatism (2010 ACR/EULAR) classification criteria for RA. Patients who have an inadequate response of at least 12 weeks to ≥ 1 conventional disease-modifying antirheumatic drugs (DMARDs) in which 1 of them is definitely methotrexate, according to their investigator judgment. Moderate to severe rheumatoid arthritis with ≥4 tender joints (of 68 joints); ≥4 swollen joints (of 66 joints); and an erythrocyte sedimentation rate (ESR) ≥30 mm/hour or a C-reactive protein level (CRP) ≥1.0 mg/dl at screening Patients discontinued all biological DMARD, including etanercept for 2 weeks or longer and infliximab, certolizumab, golimumab or adalimumab for 8 weeks or longer because of side effects, lack of compliance or lack of response. Ability to comprehend and willingness to sign the Informed Consent Form for this study

Exclusion criteria:

Active tuberculosis or Patients testing positive for latent tuberculosis (PPD > abnormal CXR) Have a history of serious allergies or a known hypersensitivity to Tocilizumab or any components of the formulations. Have an active hepatitis B or C or positive hepatitis B surface antigen or hepatitis C antibody. Have a known history of infection with human immunodeficiency virus (HIV). Patients who are weighing ≥ 100 kg Patients who had thrombocytopenia (platelet count < 100,000/µl) or Leucopenia (ANC<2,000/µl or white blood cell count < 3,500/µl). Patients with hemoglobin level less than 8.5 g/dl. Patients with aspartate transaminase (AST), alanine transaminase (ALT) 1.5-fold the upper limit of normal. 9) Patients with Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis. (Class IV: Advanced persistent limitation inability to perform usual self-care, vocational, and avocational activities). Patients who have been received previous treatment with Tocilizumab Patients who had received plasmapheresis or major surgery (including joint surgery, major cardiovascular surgery except for revascularization) within 8 weeks before entering study or planned major surgery within 6 months after entering the study. Patients who had previously received Rituximab. Patients who had received oral glucocorticoids at a dosage of > 10 mg/day of prednisolone or equivalent; or had a dose increase, new administration, or intravenous, intraarticular or intramuscular injections of glucocorticoids within 4 weeks of Tocilizumab treatment. Patients who had dose changes or added-in DMARDs or immunosuppressants within 4 weeks of Tocilizumab treatment. Immunization with a live/attenuated vaccine less than 4 weeks before baseline or planning to receive a live vaccine during the study. Women who are pregnant, breastfeeding or planning to become pregnant during the study. Patients who have stopped previous MTX treatment due to hepatotoxicity. Patients with an active infection or who have had a serious infection or have been treated with intravenous antibiotics for an infection within 8 weeks or oral antibiotics within 2 weeks prior to screening. Having history of any malignancy within the previous 5 years prior to Screening. Having history of demyelinating disorders including multiple sclerosis. Patients with a certain history of gastrointestinal disorders such as diverticulitis, active peptic ulcer or active duodenal ulcer which have been approved by a gastroenterologist. Patients who had GFR< 60 ml/min/1.73 m2 Having any other disease or disorder which, in the opinion of the Investigator, will put the subject at risk if they are enrolled.

Target sample size: 206